The overall hypothesis underlying this project is that abnormalities in polymorphonuclear cell (PMN) function in localized juvenile periodontitis (LJP) may not be an intrinsic cell associated abnormality, but rather, a consequence of exposure to quantitatively small but biologically significant elevations in cytokines or inflammatory proteins. Systemic elevations in cytokines may result from macrophage hyper-responsiveness to bacterial challenge. Recent work from our laboratory and others has demonstrated that cytokines that are primarily derived from macrophages, modulate cellular functions of PMNs from healthy subjects (HS). Specifically, these cytokines decrease PMN chemotaxis, decrease the number of surface chemoattractant receptors (FMLP and C5a), increase adherence- related molecules, induce increased level of basal oxidative metabolism and degranulation. PMNs obtained from LJP patients also exhibit functional similarities to those of cytokine treated healthy PMNs. Moreover, sera from more than 90% of the LJP patients tested, have the ability to alter functions of HS-PMNs; and this modulation of PMN function can be in part be neutralized by anti IL-1 and TNF polyclonal antibodies. Therefore, we hypothesize that the host response in LJP patients is characterized by increased production of cytokines by the monocytic/macrophage lineage of cells. A direct consequence of elevated systemic cytokine levels would be altered PMN functions, including decreased PMN chemotaxis. The present study therefore proposes to (1) delineate mechanisms of PMN dysfunction in LJP and evaluate the effect of inflammatory mediators on modulation of PMN functions. (2) quantitate and compare relative levels of cytokines present in LJP, adult periodontitis (APP) and HS sera and identify mediators responsible for the modulation of PMN function in LJP-sera by neutralizing the activity with individual or a combination of antibodies to specific cytokines. (3) compare the total and biologically active cytokine secretion in activated monocytes from patients with LJP, APP and HS. (4) quantitate and compare the relative levels of cytokine specific mRNA expression during macrophage activation in LJP, HS and APP. Since all of the elements of immune response appear to be under a complex series of regulatory controls, it is reasonable to expect that a slight alteration in triggering of the terminal inflammatory mediators can alter the host immune response. Understanding the nature of alterations in cytokine-mediated regulatory processes may permit the manipulation of these processes in a predictable manner for the benefit of an affected patient.